Schistosoma mansoni: preclinical studies with 9-acridanone-hydrazones in Cebus monkeys experimentally infected

Coelho, Paulo Marcos Zech; Pereira, Leógenes Horácio

doi:10.1590/S0036-46651991000100010

Abstracts

Derivatives of acridine (9-Acridanone-hydrazones) were tested in Cebus monkeys experimentally infected with Schistosoma mansoni, at the dosages of 50, 25, and 12.5 mg/kg (p.o., single dose). At least, four compounds seemed to be very promising, promoting alterations in the oogram and reducing the worm burden drastically, even at the lowest dose (12.5 mg/kg). No side effects could be detected after drug administration.

Schistosoma mansoni; Chemotherapy; Cebus monkeys; 9-Acridanone-hydrazones; Active drug

Derivados de acridina (9-acridanona-hidrazonas) foram testados em macacos Cebus experimentalmente infectados com Schistosoma mansoni, nas doses de 50, 25 e 12,5 mg/kg, em dose única, via oral. Quatro compostos, pelo menos, mostraram-se muito promissores, causando alterações no oograma e reduzindo drasticamente a carga de vermes, mesmo quando a dose mais baixa (12,5 mg/kg) foi usada. Efeitos colaterais não foram detectados após administração da droga.

TECHNICAL ASSAYS

Schistosoma mansoni: preclinical studies with 9-acridanone-hydrazones in Cebus monkeys experimentally infected

Schistosoma mansoni: estudos pré-clínicos com 9-acridanona-hidrazonas em macacos Cebus experimentalmente infectados

Paulo Marcos Zech Coelho; Leógenes Horácio Pereira

Departamento de Parasitologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais (ICB/UFMG). Belo Horizonte, Minas Gerais, Brasil

^{Address for correspondence} Address for correspondence: Prof. Paulo Marcos Z. Coelho Departamento de Parasitología, ICB/UFMG CP 2486 30161 Belo Horizonte, MG, Brasil

SUMMARY

Derivatives of acridine (9-Acridanone-hydrazones) were tested in Cebus monkeys experimentally infected with Schistosoma mansoni, at the dosages of 50, 25, and 12.5 mg/kg (p.o., single dose). At least, four compounds seemed to be very promising, promoting alterations in the oogram and reducing the worm burden drastically, even at the lowest dose (12.5 mg/kg). No side effects could be detected after drug administration.

Key words: Schistosoma mansoni; Chemotherapy; Cebus monkeys; 9-Acridanone-hydrazones; Active drug.

RESUMO

Derivados de acridina (9-acridanona-hidrazonas) foram testados em macacos Cebus experimentalmente infectados com Schistosoma mansoni, nas doses de 50, 25 e 12,5 mg/kg, em dose única, via oral. Quatro compostos, pelo menos, mostraram-se muito promissores, causando alterações no oograma e reduzindo drasticamente a carga de vermes, mesmo quando a dose mais baixa (12,5 mg/kg) foi usada. Efeitos colaterais não foram detectados após administração da droga.

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ACKNOWLEDGEMENT

We thank Dr. H. R. Stohler (F. Hoffmann-La Roche & Co. Ltd., Basle, Switzerland) for providing compounds used in this research, as well as for financial support and advice; Dr. Faiçal Simon and Dr. Adayr Mafuz Saliba (Fundação Parque Zoológico de São Paulo) for the supply of Cebus monkeys utilized in this study; Mr. Adelino Ferreira, Mrs. Alice N. Faria, Mr. Alberto G. Santos, Mr. Maurício V. Costa, and Miss Zenir de Souza for technical assistance.

Recebido para publicação em 16/5/1990.

Aceito para publicação em 13/9/1990.

1. ARAÚJO, N.; KATZ, N.; DIAS, E.P. & SOUZA, C.P. Susceptibility to chemotherapeutic agents of strains of Schistosoma mansoni isolated from treated and untreated patients. Amer. J. trop. Med. Hyg., 29: 890-894,1980.
2. COLES, J.C. & BRUCE, J.J. In vitro selection of drug resistant to Schistosoma mansoni. Int. J. Parasit., 17: 767-771, 1987.
3. DIAS, L.C.S.; PEDRO, R.J.; RIGO, E.; GOTO, M.M.F. & MAFRA, G.L. Linhagem humana de Schistosoma mansoni resistente a esquistossomicidas. Rev. Saúde públ. (S. Paulo), 12: 110,1978.
4. DIAS, L.C.S.; BRUCE, J.I. & COLES, O.C. Variation in response of Schistosoma mansoni strains to schistosomicides. Rev. Inst. Med. trop. S. Paulo, 30: 81-85, 1988.
5. FAIRLEY, N.H. Schistosomiasis and some of its problems. Trans. roy. Soc. trop. Med. Hyg., 45: 279-303,1951.
6. FRIEDHEIM, E.A.H.The evaluation of drugs in human schistosomiasis. Trans. roy. Soc. trop. Med. Hyg., 61: 575-579, 1967.
7. JANSMA, W.B.; ROGERS, S.H.; LIN, C.C. & BUEDING, E. Experimentally produced resistance of Schistosoma mansoni to hycanthone. Amer. J. trop. Med. Hyg., 26: 926-936, 1977.
8. KATZ, N.; DIAS, E.P.; ARAÚJO, N. & SOUZA, C.P. Estudo de uma cepa humana de Schistosoma mansoni resistente a agentes esquistossomicidas. Rev. Soc. bras. Med. trop., 7: 381-387, 1973.
9. KATZ, N. & PELLEGRINO, J. Estudos de alguns aspectos da esquistossomose mansoni em macacos Cebus pelo método de oograma quantitativo. Rev. Inst. Med. trop. S.Paulo, 16: 245-252,1973.
10. KATZ, N.; PELLEGRINO, J. & POMPEU MEMORIA, J.M. Quantitative oogram method in Cebus monkeys experimentally infected with Schistosoma mansoni. J. Parasit., 52: 917-919, 1966.
11. PELLEGRINO, J. & KATZ, N. Experimental chemotherapy of Schistosomiasis mansoni. Advanc. Parasit., 6: 233-290, 1968.
12. PELLEGRINO, J.; KATZ, N.; OLIVEIRA, C.A. & OKABE, K. Rectal biopsy and mucosal curettage in Cebus monkeys experimentally infected with Schistosoma mansoni and Schistosoma japonicum. J. Parasit., 51: 683-684, 1965.
13. PELLEGRINO, J. & SIQUEIRA, A.F. Técnica de perfusăo para colheita de Schistosoma mansoni em cobaias experimentalmente infestadas. Rev. bras. Malar., 8: 589-597, 1956.
14. ROGER, S. & BUEDING, E. Hycanthone Resistance: Development in Schistosoma mansoni. Science, 172: 1057-1058, 1971.
15. SILVA, L.C. da; HOSHINO-SHIMIZU, S.; KANAMURA, H.; STRASMANN, P.G.; CAMARGO, M.E.; SETTE Jr., H.; LOPES, J.D.; CHAMONE, D.A.F.; RAIA, S.S. & SILVA, G.R. da Serum antibody changes after repeated chemotherapic series in "parasitologically cured" patients with schistosomiasis mansoni. Rev. Inst. Med. trop. S. Paulo, 18: 206-210, 1976.
16. STOHLER, H.R. & MONTAVON, M. 9-Acridanone-hydrazones, a Novel Class of Broad-Spectrum Schistosomicidal Agents. In: INTER. CONGR. TROP. MED. MALAR., 11., Calgary, Canadá, 1984. Abstracts, p. 16-22.
17. STURROCK, R.F.; BAIN, J.; WEBBE, G.; DOENHOFF, M.J. & STOHLER, H. Parasitological evaluation of curative and subcurative doses of 9-acridanone-hydrazone drugs against Schistosoma mansoni in baboons, and observations on changes in serum levels of anti-egg antibodies detected by ELISA. Trans. roy. Soc. trop. Med. Hyg., 81: 188-192, 1987.
18. WHO Esquistosomiasis: epidemiologia y lucha. Informe de un Comité de Expertos de la OMS. Org. mund. Salud Ser. Inf. técn., (643): 1-67, 1980.

Address for correspondence:

Prof. Paulo Marcos Z. Coelho

Departamento de Parasitología, ICB/UFMG

CP 2486

30161 Belo Horizonte, MG, Brasil

Publication Dates

Publication in this collection
12 Sept 2006
Date of issue
Feb 1991

History

Received
16 May 1990
Accepted
13 Sept 1990

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

[1] 1. ARAÚJO, N.; KATZ, N.; DIAS, E.P. & SOUZA, C.P. Susceptibility to chemotherapeutic agents of strains of Schistosoma mansoni isolated from treated and untreated patients. Amer. J. trop. Med. Hyg., 29: 890-894,1980.

[2] 2. COLES, J.C. & BRUCE, J.J. In vitro selection of drug resistant to Schistosoma mansoni. Int. J. Parasit., 17: 767-771, 1987.

[3] 3. DIAS, L.C.S.; PEDRO, R.J.; RIGO, E.; GOTO, M.M.F. & MAFRA, G.L. Linhagem humana de Schistosoma mansoni resistente a esquistossomicidas. Rev. Saúde públ. (S. Paulo), 12: 110,1978.

[4] 4. DIAS, L.C.S.; BRUCE, J.I. & COLES, O.C. Variation in response of Schistosoma mansoni strains to schistosomicides. Rev. Inst. Med. trop. S. Paulo, 30: 81-85, 1988.

[5] 5. FAIRLEY, N.H. Schistosomiasis and some of its problems. Trans. roy. Soc. trop. Med. Hyg., 45: 279-303,1951.

[6] 6. FRIEDHEIM, E.A.H.The evaluation of drugs in human schistosomiasis. Trans. roy. Soc. trop. Med. Hyg., 61: 575-579, 1967.

[7] 7. JANSMA, W.B.; ROGERS, S.H.; LIN, C.C. & BUEDING, E. Experimentally produced resistance of Schistosoma mansoni to hycanthone. Amer. J. trop. Med. Hyg., 26: 926-936, 1977.

[8] 8. KATZ, N.; DIAS, E.P.; ARAÚJO, N. & SOUZA, C.P. Estudo de uma cepa humana de Schistosoma mansoni resistente a agentes esquistossomicidas. Rev. Soc. bras. Med. trop., 7: 381-387, 1973.

[9] 9. KATZ, N. & PELLEGRINO, J. Estudos de alguns aspectos da esquistossomose mansoni em macacos Cebus pelo método de oograma quantitativo. Rev. Inst. Med. trop. S.Paulo, 16: 245-252,1973.

[10] 10. KATZ, N.; PELLEGRINO, J. & POMPEU MEMORIA, J.M. Quantitative oogram method in Cebus monkeys experimentally infected with Schistosoma mansoni. J. Parasit., 52: 917-919, 1966.

[11] 11. PELLEGRINO, J. & KATZ, N. Experimental chemotherapy of Schistosomiasis mansoni. Advanc. Parasit., 6: 233-290, 1968.

[12] 12. PELLEGRINO, J.; KATZ, N.; OLIVEIRA, C.A. & OKABE, K. Rectal biopsy and mucosal curettage in Cebus monkeys experimentally infected with Schistosoma mansoni and Schistosoma japonicum. J. Parasit., 51: 683-684, 1965.

[13] 13. PELLEGRINO, J. & SIQUEIRA, A.F. Técnica de perfusăo para colheita de Schistosoma mansoni em cobaias experimentalmente infestadas. Rev. bras. Malar., 8: 589-597, 1956.

[14] 14. ROGER, S. & BUEDING, E. Hycanthone Resistance: Development in Schistosoma mansoni. Science, 172: 1057-1058, 1971.

[15] 15. SILVA, L.C. da; HOSHINO-SHIMIZU, S.; KANAMURA, H.; STRASMANN, P.G.; CAMARGO, M.E.; SETTE Jr., H.; LOPES, J.D.; CHAMONE, D.A.F.; RAIA, S.S. & SILVA, G.R. da Serum antibody changes after repeated chemotherapic series in "parasitologically cured" patients with schistosomiasis mansoni. Rev. Inst. Med. trop. S. Paulo, 18: 206-210, 1976.

[16] 16. STOHLER, H.R. & MONTAVON, M. 9-Acridanone-hydrazones, a Novel Class of Broad-Spectrum Schistosomicidal Agents. In: INTER. CONGR. TROP. MED. MALAR., 11., Calgary, Canadá, 1984. Abstracts, p. 16-22.

[17] 17. STURROCK, R.F.; BAIN, J.; WEBBE, G.; DOENHOFF, M.J. & STOHLER, H. Parasitological evaluation of curative and subcurative doses of 9-acridanone-hydrazone drugs against Schistosoma mansoni in baboons, and observations on changes in serum levels of anti-egg antibodies detected by ELISA. Trans. roy. Soc. trop. Med. Hyg., 81: 188-192, 1987.

[18] 18. WHO Esquistosomiasis: epidemiologia y lucha. Informe de un Comité de Expertos de la OMS. Org. mund. Salud Ser. Inf. técn., (643): 1-67, 1980.

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